United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland, USA.
Toxicol Mech Methods. 2002;12(4):293-300. doi: 10.1080/15376520208951165.
The CD1-haired mouse and the SKH-hairless mouse are two animal models that have been used to evaluate sulfur mustard (HD) exposure and protection in our laboratory. In a recent study we observed that a substance P inhibitor protected the haired mouse ear against an HD solution, but the same drug was not successful in protecting the hairless mouse against HD vapor. This experiment prompted us to compare HD exposures between these models. We determined the (14)C content in the skin after exposures to HD containing (14)C-HD. Rate curves were generated for applications of (1) HD in methylene chloride to the haired mouse ear; (2) HD in methylene chloride to the hairless mouse dorsal skin; and (3) saturated HD vapor to the hairless mouse dorsal skin for 6 min. The curves showed a reduction in (14)C disintegrations per min in animals euthanized 0 to 2 h postexposure. The largest percentage of decrease of (14)C content in skin occurred within 30 min of HD challenge for all exposures. An 8-mm skin-punch biopsy and a 14-mm annular skin section surrounding the region of the 8-mm skin punch were taken from the hairless mouse dorsal skin exposed to HD in methylene chloride. The ratio of the (14)C content in the 8-mm skin punch to that in the surrounding 14-mm annular skin section was 7.3, demonstrating that the HD application spreads beyond the initially biopsied site. A concentration/time value of 6.3 mug/cm(2)/min was determined by counting skin (14)C disintegrations per minute in animals euthanized immediately after exposure to saturated HD vapor. Determinations of the amount of HD showed that similar quantities of HD, 0.4 mg, were detected on each model. These results contribute to a better quantitative understanding of HD application in the haired and hairless mouse models.
CD1 毛鼠和 SKH 无毛鼠是我们实验室用来评估硫芥(HD)暴露和保护的两种动物模型。在最近的一项研究中,我们观察到一种物质 P 抑制剂可保护有毛鼠耳朵免受 HD 溶液的侵害,但相同的药物未能成功保护无毛鼠免受 HD 蒸气的侵害。这项实验促使我们比较了这两种模型中的 HD 暴露情况。我们通过测定暴露于含(14)C-HD 的 HD 后皮肤中的(14)C 含量来确定。生成了以下暴露于模型的速率曲线:(1)二氯甲烷中的 HD 作用于有毛鼠耳;(2)二氯甲烷中的 HD 作用于无毛鼠背部皮肤;(3)饱和 HD 蒸气作用于无毛鼠背部皮肤 6 分钟。曲线显示,暴露后 0 至 2 小时处死的动物的(14)C 每分钟衰变减少。对于所有暴露,(14)C 含量的最大百分比减少发生在 HD 暴露后 30 分钟内。从用二氯甲烷暴露于 HD 的无毛鼠背部皮肤中取出 8mm 皮肤活检和围绕 8mm 皮肤活检区域的 14mm 环形皮肤切片。将 8mm 皮肤活检处的(14)C 含量与周围 14mm 环形皮肤切片处的(14)C 含量之比为 7.3,表明 HD 应用的范围超出了最初活检的部位。通过对立即暴露于饱和 HD 蒸气后处死的动物进行皮肤每分钟(14)C 衰变计数,确定了皮肤(14)C 每分钟衰变计数的浓度/时间值为 6.3μg/cm(2)/min。通过检测每个模型上的 HD 量,确定了类似数量的 HD(0.4mg)。这些结果有助于更好地定量理解有毛和无毛鼠模型中 HD 的应用。